Iktos developed a cutting-edge, state-of-the-art AI-driven retrosynthesis algorithm, implemented in our in-house platform Spaya [1, 2]. Our retrosynthesis algorithm explores plausible synthetic routes under a set of search parameters defined by the user, and returns two metrics:
- a Retrosynthesis score: ranging between 0 and 1, this score reflects synthetic accessibility. The higher, the better.
- the number of Retrosynthesis steps: number of synthetic steps of the shortest and best scored route found by Spaya. The lower, the better.
Even if you do not created your own set of Retrosynthesis parameters, the Default retrosynthesis scoring is always available for selection in Scorers or in Generators set-up.
Search parameters
To get the most relevant scores with respect to their synthesis constraints, users can choose from a large number of search parameters:
- Max Steps: the maximum number of synthetic steps of synthetic routes.
- Avoid Regioselectivity: avoid synthetic routes where a regioselectivity risk has been identified.
- Max Price Per Gram: the maximum price for all starting materials, in $ / gram.
- Max Delivery Days: the maximum number of delivery days for starting materials from providers. Note: the delivery duration information is provided by commercial providers, and does not take into account the region where the user is located.
- Packaging: limit the class of starting materials that are considered.
- Providers: select from a list of commercial providers the ones whose available starting materials will be considered.
- Name reaction: select the name reactions that should be the only ones present in the synthetic routes ("Only"), forbidden to occur in the synthetic routes ("Forbidden"), or from which at least one should occur in the route ("At Least").
- Intermediates: the synthetic intermediates that needs to be present in the synthetic routes that are explored. Can be useful to orient the synthesis to specific reactions; for example, the intermediate shown in the search parameters above was found in a synthetic route for the molecule Danuglipron with a step of ring closure, so putting it as an intermediate for analogs of Danuglipron forces the algorithm to explore routes with a similar ring closure.
- Substructures: specify substructures that are imposed or forbidden in the retrosynthesis results.
If too many constraining parameters are selected, the algorithm is more likely to fail at exploring available synthetic routes and return a null Retrosynthesis score.
References
[1] Medcalf M, Jain V, Gamboa S, Atwood B, Lhuillier-Akakpo M, Cachoux V, et al. Overcoming DMTA Cycle Challenges: A Unified AI-Driven System for Efficient Drug Design . ChemRxiv. 2025; doi:10.26434/chemrxiv-2024-0z7g6-v2
[2] Parrot, M., Tajmouati, H., da Silva, V.B.R. Integrating synthetic accessibility with AI-based generative drug design. J Cheminform 15, 83 (2023). https://doi.org/10.1186/s13321-023-00742-8